Sabrina Plitt

Factors associated with vaccine failure and vertical transmission of hepatitis B among a cohort of Canadian mothers and infants.

Summary.u2002 Mother‐to‐child transmission of hepatitis B virus (HBV) continues to occur despite immunoprophylaxis. We examined maternal factors contributing to transmission in infants receiving adequate immunoprophylaxis in Alberta, Canada. Prenatal specimens from HBsAg‐positive women whose babies developed HBV infection despite immunoprophylaxis (cases) and HBsAg‐positive mothers whose babies did not (controls) were tested for HBsAg, HBeAg and HBV DNA. Specimens with detectable DNA underwent HBV genotyping. Routinely collected surveillance data and laboratory test results were compared between cases and controls. Twelve cases and 52 controls were selected from a provincial registry from 2000 to 2005. At the time of prenatal screening, median maternal age was 31u2003years [interquartile range (IQR): 27.5–34.5], and median gestational age was 12u2003weeks (IQR 10.0–15.5). Cases were more likely than controls to test positive for HBeAg (77.8%vs 23.1%; Pu2003<u20030.05). Of all mothers with detectable viral load (nu2003=u200351), cases had a significantly higher median viral load than did controls (5.6u2003×u2003108u2003IU/mL vs 1750u2003IU/mL, Pu2003<u20030.0001). Of the two cases who were HBeAg negative, one had an undetectable viral load 8u2003months prior to delivery and a sP120T mutation. The viral load in the other case was 14u2003000u2003IU/mL. The majority of isolates were genotype B (31.3%) and C (31.3%) with no significant differences in genotype between cases or controls. In this case–control study, transmission of HBV to infants was more likely to occur in mothers positive for HBeAg and with high HBV DNA.

Evidence for Increased Chlamydia Case Finding After the Introduction of Rectal Screening Among Women Attending 2 Canadian Sexually Transmitted Infection Clinics

BACKGROUNDnChlamydia trachomatis is the most common notifiable disease in Canada, and extragenital sites are believed to serve as hidden reservoirs for ongoing transmission of infection. There are no specific Canadian screening guidelines for asymptomatic individuals from extragenital sites. We sought to determine the prevalence and factors associated with rectal C. trachomatis among female sexually transmitted infection (STI) clinic attendees in Alberta, Canada.nnnMETHODSnBetween 20 July and 31 December 2012, all female attendees at 2 Provincial STI clinics receiving a pelvic examination, regardless of a history of anal intercourse, were screened for rectal C. trachomatis using the Gen-Probe Aptima COMBO 2 Assay. Demographic and behavior variables were compared between rectal-only chlamydia cases and genitourinary cases using χ(2) or Fisher exact test, Mann-Whitney test, and logistic regression.nnnRESULTSnA total of 3055 women were screened for rectal chlamydia. The prevalence of rectal chlamydia ranged from 11.7% to 13.5%. There were 133 rectal-only cases, increasing case detection by 44.3% from 300 genitourinary cases to 433 total cases, ranging from 21.7% to 88.2% by clinic. Women who were a contact to an STI were less likely to have rectal-only chlamydia for both clinics (P ≤ .001).nnnCONCLUSIONSnOur findings add to the growing body of evidence supporting universal rectal screening in high-risk women such as those undergoing pelvic exams at STI clinics.

Rapid HIV tests in acute care settings in an area of low HIV prevalence in Canada

Rapid HIV testing has the potential to improve medical care and reduce the transmission of infection. In this study, rapid HIV testing was performed on serum samples in acute care settings in five hospitals from urban and rural regions using the INSTI™ HIV-1/HIV-2 Rapid Antibody Test (bioLytical Laboratories, Richmond, British Columbia). Parallel standard HIV antibody tests were performed at the provincial reference laboratory. Patient demographics, indication for testing and risk behaviours were collected. From April 30, 2007 and November 23, 2009, 1708 individuals were tested: 875 (50.3%) tests in pregnant women, 730 (42%) in source individuals in blood and body fluid exposures and 119 (5.8%) in acutely ill persons. Twenty-five (1.4%) samples were reactive by rapid HIV testing, of which 13 were reactive previously and 1 was a false reactive. Sensitivity of the rapid HIV test compared to standard HIV testing was 100%, specificity was 99.9%, the positive predictive value was 96% and the negative predictive value was 100%. The median time from specimen collection to availability of the rapid HIV result varied by site and ranged from 54 min to 1h 42 min. In this study, the INSTI™ HIV-1 Rapid Antibody test identified reactive and non-reactive samples with similar accuracy to the conventional testing algorithm and provided a reliable way to perform rapid HIV testing in acute care settings.

Determination of the relative economic impact of different molecular-based laboratory algorithms for respiratory viral pathogen detection, including Pandemic (H1N1), using a secure web based platform

BackgroundDuring period of crisis, laboratory planners may be faced with a need to make operational and clinical decisions in the face of limited information. To avoid this dilemma, our laboratory utilizes a secure web based platform, Data Integration for Alberta Laboratories (DIAL) to make near real-time decisions.This manuscript utilizes the data collected by DIAL as well as laboratory test cost modeling to identify the relative economic impact of four proposed scenarios of testing for Pandemic H1N1 (2009) and other respiratory viral pathogens.MethodsHistorical data was collected from the two waves of the pandemic using DIAL. Four proposed molecular testing scenarios were generated: A) Luminex respiratory virus panel (RVP) first with/without US centers for Disease Control Influenza A Matrix gene assay (CDC-M), B) CDC-M first with/without RVP, C) RVP only, and D) CDC-M only. Relative cost estimates of different testing algorithm were generated from a review of historical costs in the lab and were based on 2009 Canadian dollars.ResultsScenarios A and B had similar costs when the rate of influenza A was low (< 10%) with higher relative cost in Scenario A with increasing incidence. Scenario A provided more information about mixed respiratory virus infection as compared with Scenario B.ConclusionsNo one approach is applicable to all conditions. Testing costs will vary depending on the test volume, prevalence of influenza A strains, as well as other circulating viruses and a more costly algorithm involving a combination of different tests may be chosen to ensure that tests results are returned to the clinician in a quicker manner. Costing should not be the only consideration for determination of laboratory algorithms.

Determining rubella immunity in pregnant Alberta women 2009-2012.

Rubella IgG levels for 157,763 pregnant women residing in Alberta between 2009 and 2012 were analyzed. As there have been no reported cases of indigenous rubella infection in Canada since 2005, there has been a lack of naturally acquired immunity, and the current prenatal population depends almost entirely on vaccine induced immunity for protection. Rubella antibody levels are significantly lower in younger maternal cohorts with 16.8% of those born prior to universal vaccination programs (1971-1980), and 33.8% of those born after (1981-1990) having IgG levels that are not considered protective (<15 IU/mL). Analysis across pregnancies showed only 35.0% of women responded with a 4-fold increase in antibody levels following post-natal vaccination. Additionally, 41.2% of women with antibody levels <15 IU/mL had previously received 2 doses of rubella containing vaccine. These discordant interpretations generate a great deal of confusion for laboratorians and physicians alike, and result in significant patient follow-up by Public Health teams. To assess the current antibody levels in the prenatal population, latent class modeling was employed to generate a two class fit model representing women with an antibody response to rubella, and women without an antibody response. The declining level of vaccine-induced antibodies in our population is disconcerting, and a combined approach from the laboratory and Public Health may be required to provide appropriate follow up for women who are truly susceptible to rubella infection.

DIAL: A Platform for real-time Laboratory Surveillance

Laboratory information systems fulfill many of the requirements for individual result management within a public health laboratory. However, access to the systems by data users, timely data extraction, integration, and data analysis are difficult tasks. These difficulties are further complicated by often having multiple laboratory results for specific analytes or related analytes per specimen tested as part of complex laboratory algorithms requiring specialized expertise for result interpretation. We describe DIAL, (Data Integration for Alberta Laboratories), a platform allowing laboratory data to be extracted, interpreted, collated and analyzed in near real-time using secure web based technology, which is adapted from CNPHI’s Canadian Early Warning System (CEWS) technology. The development of DIAL represents a major technical advancement in the public health information management domain, building capacity for laboratory based surveillance.

Pregnancy and Neonatal Outcomes of Women With Reactive Syphilis Serology in Alberta, 2002 to 2006

OBJECTIVESnTo describe the maternal characteristics, diagnosis, and pregnancy, and the neonatal outcomes of pregnant women with reactive syphilis serology in a Canadian cohort.nnnMETHODSnWe conducted a retrospective chart review of pregnant women in Alberta with reactive syphilis serology between 2002 and 2006. Clinical staging of syphilis in mothers and infants was determined using provincial and national surveillance criteria.nnnRESULTSnSeventy-five pregnancies met the inclusion criteria. Thirty women were adequately treated pre-conception, 20 women had infectious syphilis (10 primary, 5 secondary, 5 early latent), 24 had late latent syphilis, and one had disease of unknown stage. Seven infants with congenital syphilis and one infant with presumed congenital syphilis were born to women with primary (n = 4), secondary (n = 2), early latent (n = 1), and unknown stage (n = 1) syphilis. Treatment was provided prior to delivery in one woman; five women did not access prenatal care. Four infants had long-term sequelae.nnnCONCLUSIONnAll infants with congenital syphilis were born to women with infectious syphilis who had limited prenatal care. Initiatives to reach women at high risk are required to decrease the incidence of congenital syphilis.

Prevalence and antibiotic resistance of Mycoplasma genitalium among STI clinic attendees in Western Canada: a cross-sectional analysis

Objectives To determine the prevalence and correlates of Mycoplasma genitalium (MG) infection among men and women, determine the prevalence of gene mutations conferring resistance and compare test performance of female specimen types. Methods A cross-sectional study was conducted on specimens collected for gonorrhoea (NG, Neisseria gonorrhoeae) and chlamydia (CT, Chlamydia trachomatis) among male and female Alberta STI clinic attendees using the M. genitalium transcription-mediated amplification-research use only test. Positive specimens were sequenced for 23SrRNA, parC and gyrA genes. Gender-stratified analysis compared test results using χ2 or Fisher’s exact test, Mann-Whitney U test and logistic regression. Female endocervical and urine specimens were compared. Results A total of 2254 individuals were tested; 53.8% (n=1212) were male. Male prevalence of MG was 5.3%; CT was 5.9% and NG was 1.8%. Correlates of male infection were a non-gonococcal urethritis diagnosis and NG coinfection. MG prevalence for women was 7.2%; CT was 5.8% and NG was 1.8%. Correlates of female infection were younger age, Indigenous/Other ethnicity and CT/NG coinfection. Nearly two-thirds of eligible specimens had mutations associated with macrolide resistance and 12.2% of specimens had a parC mutation signifying possible moxifloxacin resistance. There was high concordance (98.1%) of results between urine and endocervical swabs. Conclusions The high prevalence of MG relative to CT and NG supports the incorporation of MG testing into routine sexually transmissible infection screening. The high rate of resistance to macrolides and moxifloxacin raises concerns about treatment options. The good concordance of results between urine and endocervical swabs supports the use of female urine specimens for testing.

P3.250 Early Diagnosis of Acute HIV Infection in STI Clinic Patients and Patients with Positive Syphilis Serology

Background We sought to determine if pooled nucleic acid testing (pNAT) for HIV RNA would identify early HIV infections in stored samples collected in 2008 from Edmonton (Canada) patients who were: (1) Seronegative for HIV antibody (HIVAb-) at the STI clinic, and (2) Seropositive for syphilis (syphAb+) with no history of a positive HIV test. Methods Using data from the Provincial Laboratory and STI clinic, an anonymized dataset with the last HIVAb- (HIVGO1/2, Abbott, AxSym +/- Western Blot) (STI clinic patients) or first syphAb+ (Architect, Abbott +/- RPR & Innolia) was constructed with: (1) All patients: age, gender, date of testing, N. gonorrhoea (NG) and C. trachomatis co-infection within 30 days of HIV/syphilis test, infectious syphilis stage, and HIV testing as of Dec 2010 and (2) STI clinic patients only: syphilis test results within 30 days of their HIVAb- test. Patients remaining HIVAb- > 180 days after the sample receipt date were excluded from HIV pNAT. The remaining samples were divided into SyphAb+ and SyphAb-subsets. Pools of 25 samples were tested using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (pNAT). Positive pools were broken down to identify positive individuals. Percentage calculations were based on patients with pNAT. Results 7954 HIVAb- patients were eligible. Of these, 2237 were retested and were HIVAb- > 180 days; 216 (10%) of this subset were SyphAb+. 5441 (95%) of the remaining patients had samples available for pNAT: 5001 were SyphAb-, 331 were SyphAb+, and 109 had no syphilis testing. Four SyphAb+ patients (0.07% of all, 1.2% of SyphAb+), all seen at STI clinic, had detectable HIV RNA using pNAT; one patient had Early Latent Syphilis and positive NG culture. Conclusions pNAT testing can be used to identify acute HIV infections in high risk populations. Patients with positive syphilis serology may be an important subset for this approach.

P3-S6.03 Seroreversion of treponemal tests in cases meeting Canadian surveillance criteria for confirmed congenital syphilis

Background Serologic tests for syphilis remain the mainstay of diagnosis. However, diagnosis of congenital syphilis is complicated by the passive transfer of maternal antibodies to the infant. Non treponemal test (NTT) titres should decline by age 3u2005months and should be non reactive by age 6u2005months if the infant was not infected or was infected but adequately treated. Limited data exist on the serologic outcome of treponemal tests (TT) in cases with clinical or laboratory evidence of congenital syphilis at birth. Methods Cases meeting Canadian surveillance criteria for confirmed early congenital syphilis [within 2u2005years of birth] (http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/35s2/Syphilis-eng.php) were reviewed from the Alberta Health Services Edmonton zone from 2005 to 2010. Under Albertas Public Health Act, maternal stage, treatment information and serologic follow-up and infant clinical, laboratory and treatment information are obtained and stored in a provincial STI database. Results 22 cases met surveillance criteria for confirmed congenital syphilis: six were either stillborn/deceased at birth, three are still under 18u2005month serologic follow-up, one had persistently reactive TT (21u2005months) and four had reactive TT at the end of their follow-up period (ages 11, 12, 13 and 15u2005months). 3/5 cases with persistently reactive TT were treated with 9–10u2005days of intravenous penicillin within 0–2u2005days of birth, 1 at 3u2005months of age and 1 at 8u2005months of age. In 4/5 of these cases, the RPR had reverted to non reactive at the end of the follow-up period while in the 5th case (treated at 8u2005months), the RPR declined from a titre of 1:4096 dilutions at birth to 1:64 dilutions at 11u2005months of age. The remaining eight cases had negative TTs, as summarised in the table. All were treated with 10u2005days of intravenous penicillin (except case #2 treated with 9u2005days) see Abstract P3-S6.03 table 1. Abstract P3-S6.03 Table 1 Seroreversion TT Congenital Syphillis Case* Maternal stage/GA at treatment Neonatal/infant diagnostic features Infant age at treatment (GA at birth) Infant age /final serologic results 1 Primary/postpartum Abnormal CSF (4) Birth (34u2009weeks) 7u2009months/RPR NR, TPPA NR, FTA-ABS NR 2 Primary/postpartum Abnormal CSF (3) Birth (unknown) 14u2009months/RPR NR, TPPA NR Abnormal long bone radiographs Intraventricular haemorrhage Fetal hydrops 3 Primary/postpartum Abnormal CSF (3) Birth (38u2009weeks) 10u2009months/syphilis EIA negative 4 Early latent/postpartum Abnormal CSF (3) Birth (30u2009weeks) 5u2009months/syphilis EIA negative 5 Early latent/34u2009weeks GA Abnormal CSF (3) Abnormal long bone radiographs Birth (37u2009weeks) 12u2009mos/syphilis EIA negative 6 Primary/postpartum Abnormal CSF (3) Birth (38u2009weeks) 18u2009months/syphilis EIA negative 7 Early latent/postpartum Abnormal CSF (4) Birth (36u2009weeks) 19u2009months/syphilis EIA negative 8 Secondary/28u2009weeks GA Abnormal CSF (4) Intrauterine anaemia, hydrops, cardiomegaly, ascites. Positive syphilis PCR from intrauterine fetal blood Birth (36u2009weeks) 13u2009months/syphilis EIA negative CSF, cerebrospinal fluid; GA, gestational age; NR, non reactive; R, reactive; EIA, enzyme immunoassay; RPR, rapid plasma reagin; TPPA,Treponema pallidum particle agglutination; FTA-ABS, fluorescent treponemal antibody absorbed; PCR, polymerase chain reaction. * Number of CSF abnormalities (elevated WBC, RBC or protein, low glucose, reactive VDRL). Conclusions As with early treatment of primary syphilis cases, seroreversion of TT can occur in cases meeting clinical and laboratory criteria for congenital syphilis. Seroreversion was observed with older TT such as TPPA and FTA-ABS as well as the newer syphilis EIA.